Hemopoiesis

08Sep07

Formation of blood cells is called hemopoiesis.

Embryonic Hemopoiesis

• First Phase
  • Occurs in blood islands in the wall of yolk sac.
• Second (Hepatic) Phase
  • Hemopoietic centers appear in the liver and lymphatic tissue.
  • Liver is the major blood forming organ for featus.
• Third Phase
  • Bone marrow, other lymphatic tissues.

After birth, hemopoiesis occurs in red bone marrow & lymphatic tissue as in adults.

Initial stages are regulated by colony stimulated factors (CSF). There are 2 types of CSF:

• Interleukins
• Inhibitory factors.

Unitarian / Monophylatic

Adult – red blood cells, granulocytes, monocytes & platelets are formed in red bone marrow.

Temporary idea of hemopoiesis (Unitarian) – all blood cells arise from a common stem cell.

Unitarian Theory

• Common stem cell gives rise to colony forming unit (CFU)
• Totipotential @ Pluripotential give rise to myeloid (“myeloid”- related to leukocytes, granulocytes) series of cells is known as CFU-S
• While lymphoid series of cells is known as CFU-Ly
• CFU are immature cell type that gives rise to all blood cells lines found in bone marrow
• CFU as stem cell, are morphologically indistinguishable (couldn’t be differentiated under microscope) from each other & from lymphocytes.

Bone Marrow

• Red Bone Marrow (Active)
  • Semi fluid consistence
  • Normally include more or less adipose cells
  • Consists of hemopoietin cells, reticular cells, reticular fibers.
  • Reticular cells
    • Many processes
    • Processes connect each other & also with hemopoietic cells and sinusoidal capillaries forming a 3-Dimensional network.
    • Appear as sponge-like matter & play a trophic role
    • Stimulate & differentiate stem cells into blood cells by secreting hormones (CSF)
  • Supporting stroma is reticular fibers.
  • Blood vessels
    • Sinusoidal capillaries
    • Venosinuses
• Yellow Bone Marrow (Inactive)
  • More widespread in adults
  • Highly infiltrated with fat
  • Is not hemopoietic
  • In general, it is adipose tissue
  • Mainly consists of adipose cells, single blood vessel.
  • Yellow marrow can revert to red blood marrow after haemorrhage to increases hemopoiesis.

Development of erythrocytes (Erythropoiesis)

• Includes some cell transformations of certain immature cells.
• Characterized cell division, accumulation of hemoglobin in cytoplasm, disappearance of cell nucleus.
• Among recognizable developing cells:
  • Polychromaphilic
    • Arise from division of basophilic erythroblasts.
    • 12-15µm in diameters
    • Round, densely stained nucleus
    • Cytoplasm : pale, mixed pink-blue colour
    • Consists of ribonucleic (blue) and hemoglobin (red)
    • Organelles are decreased in number
    • Last stage of division occurs.
  • Normoblast
    • Small cells (8-12µm)
    • Dark-blue nucleus
    • Pink cytoplasm – large amount of hemoglobin
    • Oxyphilic
    • Loses its nucleus by extruding it from cell
    • Mature erythrocyte passed in blood through capillary wall
    • Number of erythrocyte produced daily : >1 Trillion
    • Number of erythrocyte released = regulation of erythropoietin
    • Erythropoietin
      • Hormone-like substance
      • Secreted by kidney
      • Response to decreased tissue-oxygen tension
    • Lifespan : 4 months

Development of granulocytes

• Derives from CFU of their own
• Promyelocytes.
  • First recognizable cells in granulapoiesis.
  • Large spherical/oval nucleus
  • Some amount of primary non-specific granules in cytoplasm
• Recognition of neutrophile, eosinophile & basophile becomes possible only in the next stage – myelocytes.
• When specific granules begin to form in cytoplasm, it is the indication of maturation.
• Myelocytes
  • Indentation of the nuclei (kidney-shaped)
  • Continue to divide to next stage : metamyelocytes
  • Due to well-developed specific granules in cytoplasm, metamylocytes differentiate into neutrophile, eosinophile and basophile.
  • Indentation of nucleus depends to form a horse-shoe shape
  • Lifespan of mature granulocytes: 8-12hours
  • Lifespan of Neutrophile : 1-2 days

Development of monocyte

• Arise from pro-monocytes
• It’s colony is formed in unit too
• Circulates in peripheral blood within 16 hours. After that, it immigrates to tissue forming macrophages.

Development of Megakaryocyte

• From megakryoblast
• Division occurs endomitotically (no daughter cells are formed)
• A single-cell nucleus become very large, multilobated, polyploid.
• The ploidy of nucleus can be up to 64n
• When megakryoblast transforms into megakaryocytes, mature cells begin to make up platelets.

Lymphopoiesis

• From lymphopoietic stem cells
  • Originated from bone marrow
  • Multipotential stem cell (CFU-Ly)
• CFU-Ly
  • 2 main branched line
    • T-Cell Line
    • B-Cell Lne
  • Divides in bone marrow forming immune-competent unipotential cells:
    • CFU-LyB
      • In birth, migrates through diverticulum (pouch from a tubular organ)
      • Attache to intestine, known as the “bursa of fabricius”
      • In absence of the bursa, development of immune-competent cells occur in a bursa-equivalent location in bone marrow & gut-associated lymphatic tissue
    • CFU-LyT
      • Undergo mitosis, transformed into immune-incompetent cells.
      • Travel In circulation to the cortex of the thymus
      • In thymus, proliferate mature & begin to express cell surface markers.
      • As the markers appear on the T-Cell + molema, it become immune-competent T-Lymphocytes.
• Clones of T & B cells are established throughout the time of birth.
• Both T & B cells proceed to lymphoid organs where they form clones.

Natural Killer (NK) Cells

• Two types
  • Antibody dependent
    • Can recognize & Kill cells that are coated with antibody
    • Mode of killing depends on:
      • Perforins: it forms pores in plasma membrane of targeted cell to allow granzymes to enter cytoplasm
      • Granzymes: induces apoptoxis (self-cell death)
  • Antibody Independent
    • Is regulated by the presence of “Kill Signal” and by the absence of “Don’t Kill Signal”
    • “Kill Signal” = specific carbohydrate chains on targeted cell surface

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